It is believed that, in mature animals, Sertoli cells and jgerm cells of the testis interact to coordinate germ cell differentiation with the biochemical activities and morphological changes, occuring in Sertoli cells, which are necessary for the success of the process of spermatogenesis. Although several models have been proposed for the mechanism of Sertoli-germ cell interaction, as yet no mechanism has been demonstrated to exist. Other workers have suggested that Sertoli cell response to FSH may be modulated by germ cells in vivo. Preliminary evidence from my laboratory shows that germ cells or germ cell membranes can directly stimulate Sertoli membrane adenylate cyclase to an extent comparable with FSH. Taken together, the results suggest the possibilities that Sertoligerm interaction may involve germ cell-dependent modulation of Sertoli response to FSH or may occur by a mechanism identical to the mechanism of peptide hormone action. Therefore, the goal of this proposal is to investigate the hypotheses that germ cells interact with mature Sertoli cells to modify FSH response or that germ cells may directly stimulate Sertoli cell adenylate cyclase to initiate a series of events identical to that initiated by FSH. The specific aims of the proposal are to determine if germ cells directly or, by modulation of FSH response, indirectly affect Sertoli cell FSH receptor numbers, adenylate cyclase activity, phosphorylation of proteins, cell morphology and distribution of cytoskeletal proteins. These aims will be approached by using, in a complementary manner, biochemical and morphological techniques applied primarily to an in vitro cell culture experimental model system. It is expected that the proposed research will contribute to our understanding of spermatogenesis and to cell-cell interaction in the testis and may ultimately lead to new avenues of approach to development of male contraceptives. Moreover, this research may reveal a previously unsuspected significance to our appreciation of the mechanism of peptide hormone action, namely that, in order to elicit responses in neighboring cells, cell-cell interaction may involve the same biochemical pathways as those affected by peptide hormones.